Project abstract for group bittermp

Translational Control in Lung Disease

These researchers seek to understand how the protein synthesis apparatus regulates gene expression and cell function. They have discovered that pathological activation of translation initiation complex eIF4F imparts primary fibroblasts and epithelial cells with autonomy for growth and survival and is required for cancer cells to maintain a malignant phenotype.

This research program addresses four major questions:
• What mechanisms govern which mRNA are selected for translation and how is it organized to mediate normal or pathological cell function? In collaboration with the Henke laboratory at Minnesota and the Larsson laboratory at the Karolinska in Stockholm, this line of investigation features genome-wide approaches in vitro and in vivo. The goal is to decipher the rules governing the translational control step in gene expression.
• Can we disable pathological feedback loops in IPF? In collaboration with the Henke laboratory, the researchers are pursuing experiments to understand how fibrosis begins and how the process can be interrupted. These studies focus on the mechanisms by which a fibrotic lung extracellular matrix can corrupt mesenchymal progenitor cells and differentiated fibroblasts to become fibrogenic.
• Is COPD on the causal pathway to cancer? The researchers are addressing this question as part of a large multi-level OMICS study of COPD lung tissue from patients with and without lung cancer. This will be the first study to integrate data from the genome, transcriptome, translatome and proteome. It is led by the Christine Wendt laboratory at Minnesota and the Yang laboratory at Mayo with collaborators from the Karolinska.
• Can we correct pathological function of the protein synthesis apparatus with small organic molecules? The Bitterman laboratory is testing novel translational repressors as potential anticancer and antifibrotic agents in collaboration with the Carston Wagner laboratory in the College of Pharmacy (Medicinal Chemistry).

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